1. Field of the Invention
This invention describes technology useful for obtaining progesterone and progesterone-related compounds from steroids having a 20-carboxamido functionality.
2. Description of the Art
It is known that progesterone and progesterone-like compounds can be made through a variety of routes. In the present invention, 20-carboxamido compounds are utilized to form progesterone and its analogs. One route utilizing an acid functionality on the steroid side chain is reported in an article entitled, "The Conversion of Hyodesoxycholic Acid to Progesterone," by Bharucha, et al, as reported in the Canadian Journal of Chemistry, Vol. 34, 1956 at page 982-990. The Bharucha, et al, route also utilizes N-bromosuccinimide as one of the reactants in this process. Another route utilizing an acid, this time a 20-carboxy acid of a steroid to obtain progesterone via the Oppenauer oxidation is reported by Wieland, et al, in Helvetica Chimica Acta, Vol. XXXII, Part VI (1949), No. 255 at page 1922-1933. Wieland again with his coauthor Mischler in Helvetica Chimica Acta, Vol. XXXII, Part V (1949), No. 233 at pages 1764-1769 again reports a method for obtaining progesterone through a complicated route utilizing a 20-carboxy steroid compound.
Julian, et al, in an article entitled, "Delta 20-pregnenes from Bisnor-Steroid Acids," as reported in JACS at Vol. LXX, published 1948, No. 3, at pages 887-892, reports that 20-carboxy steroids may be converted to useful steroids. In another article published in Helvetica Chimica Acta at Vol. XXXII, Part V (1949), No. 232 at pages 1758-1763, Meystre, et al, report that 20-carboxy steroid compounds may be converted to the corresponding chloroamine and thereafter, through a multistep reaction, progesterone may be obtained. U.S. Pat. No. 3,519,658 issued to Adam, et al, July 7, 1970 discusses the use of N-chlorosuccinimide with steroids.
Useful steroids having a 20-carboxyl functionality are described in European Patent application 4-913 published Oct. 31, 1979. An additional useful product obtained therein is 3-oxo-pregna-1,4,17(20)- triene-20-carboxylic acid. More useful acids are described in U.S. Pat. No. 3,994,933 issued to Jiu, et al, Nov. 30, 1976.
The present invention, however, overcomes a number of difficulties involved in the previous reactions in that the progesterone may be obtained directly without protection of the unsaturation in the A ring of the steroid structure and without the need to utilize chemical compounds to protect or interconvert the 3-keto functionality on the A ring.
Throughout the specification and claims, percentages and ratios are given by weight and temperatures are in degrees Celsius unless otherwise indicated.